Glucocorticosteroids having anti-inflammatory properties are widely used for the treatment of inflammatory conditions or disorders of skin, airways, eye, GI tract, joints, CNS etc, and several autoimmune disorders. Some of the inflammatory skin disorders where treatment with glucocorticoids is prescribed are eczema, psoriasis, allergic dermatitis, pruritis, hypersensitivity reactions etc. Inflammatory or allergic conditions of the airways for which glucocorticoids are used include disorders of nose, throat or lungs such as rhinitis (including hay fever), nasal polyps, asthma (including allergen-induced asthmatic reaction), chronic obstructive pulmonary disease (COPD), interstitial lung disease, fibrosis, etc. Glucocorticoid administration is also used for inflammatory bowel disorders such as ulcerative colitis and Crohn's diseases; and inflammatory joint disorders such as rheumatoid arthritis which are autoimmune diseases.
However, administration of corticosteroids in general may cause, in addition to the desired pharmacological effect, undesirable or adverse side effects at sites distant from the target tissue, the so-called systemic effects. Some of the undesired systemic effects encountered include widespread immunosuppression, increased bone turnover, impaired growth, skin thinning, diabetes, obesity, water retention, progesterone and estrogen related disorders. It is therefore desirable to have glucocorticoids which possess potent anti-inflammatory activity at the target tissue, with minimal or preferably no systemic activity at therapeutic doses when used for chronic treatment.
Our interest to develop compounds which act at the specific site of inflammation with insignificant or no noteworthy side effects has led us to the discovery of novel, safe 11β-hydroxyandrosta-4-ene-3-one compounds described in U.S. Pat. No. 8,785,425 and PCT application WO2014192027. These compounds possess useful anti-inflammatory activity whilst having insignificant or no noteworthy systemic side effects at multiples of efficacious dose. WO 2014192027 specifically discloses a compound of Formula I
which substantially meets the desired attributes, i.e. good anti-inflammatory effects at the target tissue whilst having insignificant or no noteworthy systemic side effects at multiples of efficacious dose. The processes disclosed in application WO2014192027 involve isolation of the compound of Formula I from a mixture of methanol and dichloromethane eluted during purification by column chromatography. The white solid obtained therein was found to be amorphous in nature. The amorphous form was found to be unstable upon storage even at ambient conditions. It is crucial to have a polymorphic form which is stable, which can be produced consistently and is suitable for the preparation of stable formulations. Thus, there is a need to develop new polymorphic form/s of the compound of Formula I which is/are stable, consistent and reproducible.